Risk of metabolic syndrome and metabolic phenotypes in relation to biomarker-calibrated estimates of energy and protein intakes: an investigation from the Women's Health Initiative

ABSTRACT Background Metabolic syndrome (MetS) is associated with increased mortality independent of BMI, resulting in discordant metabolic phenotypes, such as metabolically healthy obese and metabolically unhealthy normal-weight individuals. Studies investigating dietary intake in MetS have reported mixed results, due in part to the limitations of self-reported measures. Objectives To investigate the role of biomarker-calibrated estimates of energy and protein in MetS and metabolic phenotypes. Methods Postmenopausal participants from the Women's Health Initiative (WHI) study who were free of MetS at baseline, had available data from FFQs at baseline, and had components of MetS at Year 3 (n = 3963) were included. Dietary energy and protein intakes were estimated using biomarker calibration methods. MetS was defined as 3 or more of the following: elevated serum triglycerides (≥150 mg/dL), low HDL cholesterol (<50 mg/dL), hypertension [systolic blood pressure (BP) ≥130 or diastolic BP ≥85 mmHg], elevated serum glucose (>100 mg/dL), and abdominal adiposity (waist circumference > 89 cm). Models were adjusted for age, WHI study component, race/ethnicity, education, income, smoking, recreational physical activity, disease history, and parity. Results For every 10% increment in total calibrated energy intake, women were at a 1.37-fold elevated risk of MetS (95% CI, 1.15–1.63); a 10% increment in calibrated total protein intake was associated with a 1.21-fold elevated risk of MetS (95% CI, 1.00–1.47). Specifically, animal protein intake was associated with MetS (OR, 1.08; 95% CI, 1.02–1.14), whereas vegetable protein intake was not (OR, 0.99; 95% CI, 0.95–1.03). No differences were seen when examining metabolic phenotypes. Conclusions We found that higher calibrated total energy, total protein, and total animal protein intakes were strongly associated with MetS. If replicated in clinical trials, these results will have implications for the promotion of energy and animal protein restrictions for the reduction of MetS risks.

Hormone Replacement Therapy: Lebanese Women’s Awareness, Perception, and Acceptance

Objectives. Hormone replacement therapy (HRT) had been the gold standard for the treatment of menopausal symptoms until the publication of the World Health Initiative (WHI) study. After the WHI study, the use of HRT changed among the physicians and patients all over the world despite newer more reassuring data. This study aimed to investigate the knowledge and attitudes of women towards HRT and the factors affecting it for better counseling. Study design. A clinic-based cross-sectional study using a survey was offered to women aged 40 years and above coming to the women’s health center at the American University of Beirut Medical Center (AUBMC) from October 1st, 2017, till March 31st, 2018. The questionnaire included questions about demographics and menopausal symptoms in addition to knowledge and attitudes towards menopause and HRT. Main outcome measures. Our main hypothesis was that women would be aware of HRT as a treatment modality; however, the majority would have a negative attitude towards its usage. Results. The response rate was 87.8%. Seventy-three percent of the respondents had already heard about HRT with 57.9% supporting the use of HRT; however, 47.9% did not know when to use it. The significant predictor for having heard about HRT and a positive attitude towards HRT were having HRT prescribed as a part of treatment and employment status, respectively. Conclusions. Lebanese women are aware of HRT as a treatment option; however, a lack of both proper information and positive attitude towards HRT use was noted.

Hormone replacement therapy and elevated breast cancer risk: An artifact of growth acceleration?

BackgroundAvailable data on accelerated proliferation and increased breast cancer risk due to hormone replacement therapy (HT) are inconsistent. Data on long-term effects of HT are limited. The interaction between several key factors was examined using a model-based approach.MethodsCohorts of 50 year old women, BCs were randomly generated for 30 years based on the age-specific incidence. A control group received a HT that increased the growth of occult BCs. In a 3rd cohort BCs were additionally induced by HT. This model illustrates the interrelationship of important parameters and allows the simulation and comparison of previously published clinical studies.ResultsUsing plausible parameters for BC growth factor (GF) and HT-related effects it was demonstrated that HT caused accelerated growth of occult BCs with an apparent increase in incidence and shortened time to diagnosis. The Women’s Health Initiative (WHI) study was reconstructed assuming a GF of 1.43 induced by HT. The decision of millions of women to discontinue or forego HT based on the published risks of the WHI-study in 2002 could explain the marked jump of 6.7% in incidence within a few months. If additional BCs were induced by HT, then these BCs may become apparent after 10 or more years together with those appearing according to the normal incidence. At this time conclusive data on type, timing, and molecular characteristics of HT induced BCs are not yet available.ConclusionThe acceleration in growth of occult BC has been underestimated. Initially HTs can cause an apparent increase in BC incidence thereby explaining the WHI-dependent decrease in 2003. A HT associated BC risk should only be detectable with a delay of ten and more years.

Osteoporosis OSTEOPOROSIS –IN OLD AGE AND GERIATRICS

In the beginning, that is from the 1960's, when a link between menopause and osteoporosis was first identified; estrogen treatment was the standard for preventing bone loss, however there was no fracture data, even though it was thought to be effective. This continued until the Women's Health Initiative (WHI) study in 2001 that published data on 6 years of treatment with hormone therapy that showed an increase in heart attacks and breast cancer. Even though the risks were small, 1 per 1500 users annually, patients were worried and there was a large drop off in estrogen use. In later analyses the WHI study showed that estrogen reduced fractures and actually prevented heart attacks in the 50-60 year age group. Estrogen alone appeared to be safer to use than estrogen + the progestin medroxyprogesterone acetate and actually reduced breast cancer.

Performance of FRAX in Predicting Fractures in US Postmenopausal Women with Varied Race and Genetic Profiles

Background: Whether the Fracture Risk Assessment Tool (FRAX) performed differently in estimating the 10-year fracture probability in women of different genetic profiling and race remained unclear. Methods: The genomic data in the Women’s Health Initiative (WHI) study was analyzed (n = 23,981). The genetic risk score (GRS) was calculated from 14 fracture-associated single nucleotide polymorphisms (SNPs) for each participant. FRAX without bone mineral density (BMD) was used to estimate fracture probability. Results: FRAX significantly overestimated the risk of major osteoporotic fracture (MOF) in the WHI study. The most significant overestimation was observed in women with low GRS (predicted/observed ratio (POR): 1.61, 95% CI: 1.45–1.79) specifically Asian women (POR: 3.5, 95% CI 2.48–4.81) and in African American women (POR: 2.59, 95% CI: 2.33–2.87). Compared to the low GRS group, the 10-year probability of MOF adjusted for the FRAX score was 21% and 30% higher in the median GRS group and high GRS group, respectively. Asian, African American, and Hispanic women respectively had a 78%, 76%, and 56% lower hazard than Caucasian women after the FRAX score was adjusted. The results were similar for hip fractures. Conclusions: Our study suggested the FRAX performance varies significantly by both genetic profile and race in postmenopausal women.

Hormontherapie in der Peri- und Postmenopause

The recently published 18-year-follow-up of the WHI-study might resolve the long-standing dispute about hormone therapy, possibly reconciling the opposing parties attributing life-threatening risks to either the administration or the withholding of hormone therapy. 16 608 women without hysterectomy had taken either combined hormone therapy with estrogen and progestin or placebo for an average of 5.2 years, while 10 739 women after hysterectomy (and bilateral ovarectomy in 40 %) had taken either estrogen therapy alone or placebo for an average of 7 years. 7489 deaths were recorded until 2014. Over both studies, mortality was 27.1 % after hormone therapy and 27.6 % after placebo. New findings on perimenopause can help towards phase-adapted and complaint-targeted hormone therapy in the future.